This Core will focus on the role of genetic susceptibility in toxic responses to environmental agents. This Core is headed by Dr. Nebert; its stated long-range goal is, "to identify and characterize genetic polymorphisms concerning differences in response to environmental agents -responses include tumorigenesis as well as acute and chronic toxicity." There are six specific aims stated for this Research Core: 1) to elucidate mechanisms of gene expression and regulation through genetic variants; 2) to screen populations and three-generation families for differences in toxic responses; 3) to determine associations between a genetic locus and a phenotypic trait; 4) to understand the molecular basis of a polymorphism; 5) to study the interaction of genes and agents during embryogenesis; and 6) to evaluate the impact of each polymorphism on human health. This Research Core was one of the four original Research Cores. In the Progress Section, the seven previous members of this Core are listed; only Nebert remains a member, while Menon joined in year 04 and Bornschein, Potter and Cartwright in year 05. Anderson and Foroud are new members. The proposed Core of seven members holds 32 current grants (seven from NIEHS) and lists 122 publications since 1992 (two with Core members as coauthors).